About Amphastar Pharmaceuticals

Amphastar Pharmaceuticals, Inc. operates as a bio-pharmaceutical company. The company focuses primarily on developing, manufacturing, marketing, and selling technically challenging generic and proprietary injectable, inhalation, and intranasal products, and insulin active pharmaceutical ingredient, or insulin API products. The company manufactures and sells over 20 products, the overwhelming majority of which are prescription pharmaceuticals. Since December 2018, the company has sold its patented Primatene MIST using a new hydrofluoroalkanes, or HFA, formulation as its sole over-the-counter product. The company’s largest products by net revenues include Primatene MIST, epinephrine, glucagon, phytonadione, lidocaine, and enoxaparin sodium. In April 2022, the FDA approved the company’s ganirelix acetate injection 250mg/0.5mL prefilled syringe, which the company launched in June 2022. In July 2022, the FDA approved the company’s vasopressin injection, USP 20 Units/mL, 1 mL single-dose vial, which the company launched in August 2022. In May 2022, the FDA approved the company’s regadenoson injection, 0.08mg/mL, 5mL, single-dose prefilled syringe. The company is developing a portfolio of generic abbreviated new drug applications, or ANDAs, biosimilar insulin product candidates and proprietary product candidates, which are in various stages of development and target a variety of indications. Three of the ANDAs and one new drug application, or NDA, are on file with the FDA. The company’s primary strategic focus is developing and commercializing products with high technical barriers to market entry. The company is specifically focused on products that leverage its proprietary research and development capabilities; require raw materials or APIs for which the company has a competitive advantage in sourcing, synthesizing, or manufacturing; and/or improve upon an existing drug’s formulation with respect to drug delivery, safety, and/or efficacy. Markets The company primarily targets products with high technical barriers to market entry, with a particular focus on the injectable and inhalation markets. The company also manufactures and sells certain APIs. Injectable Market: The company’s generic development portfolio is targeting opportunities in over $16 billion of this market. Inhalation Market: The company’s generic development portfolio is targeting opportunities in over $6 billion of this market. Strategy The company is pursuing the following key strategies: diversify the company’s revenues by commercializing its product candidates; focusing on high-margin generic product opportunities; developing proprietary products; leveraging the company’s vertically integrated infrastructure to drive operational efficiencies; and targeting and integrating the acquisitions of pharmaceutical companies, products, and technologies. Technical Capabilities The company develops, manufactures, markets, and sells generic and proprietary products that utilize injectable, inhalation, and intranasal delivery systems. The company also manufactures and sells insulin API. Injectable: The company’s injectable product technologies enable the company to develop and manufacture generic and proprietary injectables in liquid, lyophilized, suspension, and emulsion forms, as well as the use of pre-filled syringes to facilitate the safety and convenience to users. The company has multiple injectable manufacturing facilities that include aseptic filling lines dedicated to the sterile production of injectable products. Additionally, the company maintains compliance with cGMP regulations, which has enabled the company to obtain regulatory approvals and support commercial supply. Inhalation and Intranasal: The company is focused on developing a broad range of generic and proprietary inhalation and intranasal products utilizing various delivery technologies. The company has expertise in formulating HFA-based MDIs and DPIs, as well as packaging the company’s inhalation drugs in blister packs and other forms, which can be used for loading the company’s products into a variety of inhalation devices. As with the company’s injectable products, the company maintains compliance with cGMP regulations, which will enable the company to obtain regulatory approvals and support commercial supply. Additionally, the company has extensive formulation and clinical experience in developing complex formulations that can be administered by intranasal delivery. Finished Pharmaceutical Products Marketed Products The company manufactures and sells over 20 products in the company’s finished pharmaceutical product segment. The following is a description of products in the company’s existing portfolio. Primatene MIST Primatene MIST, an over-the-counter epinephrine inhalation product, is indicated for the temporary relief of mild symptoms of intermittent asthma. The company developed an HFA version of Primatene MIST to replace the over-the-counter CFC formulation of the company’s Primatene MIST product, which was withdrawn for environmental reasons under the Montreal Protocol. Glucagon for Injection Emergency Kit Glucagon for injection is a difficult to manufacture injectable product. The company received the first-ever FDA approval of a generic version of rDNA Glucagon in the fourth quarter of 2020. Using a dedicated process and sophisticated characterization technology, the company demonstrated to the FDA that its highly purified synthetic peptide product is bioequivalent and therapeutically equivalent to the reference listed drug, or RLD, which is an rDNA product. Glucagon for injection emergency kit is indicated for the treatment of severe hypoglycemia and for use as a diagnostic aid. Enoxaparin Enoxaparin is a difficult to manufacture injectable form of low molecular weight heparin which is used as an anticoagulant, and has multiple indications, including the prevention and treatment of deep vein thrombosis. Enoxaparin is difficult to produce in part because the API is not easily obtained or manufactured. The company manufactures the API for its enoxaparin product and perform all subsequent manufacturing of the finished product in-house. Naloxone The company sells two versions of naloxone injections indicated for the emergency treatment of known or suspected opioid overdose. Other Marketed Products Other finished pharmaceutical products that the company markets include the following: Cortrosyn (cosyntropin for injection), a lyophilized powder that is indicated for use as a diagnostic agent in the screening of patients with adrenocortical insufficiency; Amphadase, a bovine-sourced hyaluronidase injection that is used as an adjuvant in subcutaneous fluid administration for achieving hydration, to increase absorption and dispersion of other injected drugs, and in subcutaneous urography for improving absorption of radiopaque agents; Epinephrine injection, indicated for emergency treatment of allergic reactions, including anaphylaxis, and to increase mean arterial blood pressure in adult patients with hypotension associated with septic shock; Lidocaine jelly, a local anesthetic product used primarily for urological procedures; Lidocaine topical solution, a local anesthetic used for a variety of procedures; Phytonadione injection, an injection of Vitamin K1 that is used for newborn babies; The company’s portfolio of emergency syringe products, including critical care drugs such as atropine, calcium chloride, dextrose, epinephrine, lidocaine, and sodium bicarbonate, are provided in pre-filled syringes and are designed for emergency use in hospital settings; Morphine injection in prefilled syringe, pain management product indicated for use with Patient Controlled Analgesia (PCA) pumps; Lorazepam injection, a sedative used prior to surgery and medical procedures; Neostigmine methylsulfate injection, a cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants, such as gallamine and tubocurarine; Isoproterenol hydrochloride injection, indicated for multiple uses, including mild or transient episodes of heart block that do not require electric shock or pacemaker therapy; Ganirelix Acetate Injection, indicated for the inhibition of premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation; and Vasopressin is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines. Product Candidates The company focuses on both generic and proprietary product candidates in the injectable, inhalable and intranasal markets. The company’s pipeline products are in various stages of development, with a number of these candidates still in the early stages of development. The company has over 20 product candidates in its pipeline, including generic ANDAs, biosimilar product candidates and proprietary product candidates. Generic Product Candidates The company generally employs a strategy of developing generic product candidates that possess a combination of factors that present technical barriers to competition, including difficult formulations, which require complex characterizations, difficult manufacturing requirements and/or limited availability of raw materials. The company has generic ANDAs and biosimilar product candidates at various development stages that leverage the company’s various technical capabilities, including injectable technologies, which include various delivery methods and sizes of pre-filled syringes, vials in solution, suspension and lyophilized forms; inhalation technologies, which include MDIs and DPIs; and sophisticated analytical technologies, including characterization and immunogenicity studies for complex molecules, particle engineering, sustained-release technology, peptide, protein and DNA analysis and synthesis. Proprietary Product Candidates The company’s integrated technical skills and expertise provide a strong basis for the development of proprietary drug candidates. These skills include new chemical entity assessment, peptide and protein synthesis technology, complex formulation development, characterization analysis and immunogenicity studies, among others. With respect to the company’s proprietary pipeline strategy, the company has proprietary drug candidates at various development stages that leverage the company’s various technical capabilities. Intranasal Naloxone Intranasal naloxone, a prescription naloxone nasal spray product candidate, is intended to be used for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. The company filed an NDA for Naloxone Hydrochloride Nasal Spray in April 2016. In February 2017, the company received a Complete Response Letter, or CRL, from the FDA, which identified four primary issues that need to be addressed prior to approval of the company’s NDA. The four issues are consisted of improving on the company’s human factor validation study, modifying the delivery accuracy verification method, improving the company’s standards of device reliability, and adjusting the volume per actuation to account for pediatric use down to birth. The company has worked with the FDA to resolve these issues, most recently in 2020 with a Face-to-Face Meeting in which a clear pathway for addressing these issues was created. In September 2022, the company responded to the CRL. The company intends to continue to work with the FDA to address their concerns described in the CRL. However, there can be no guarantee that the company’s response to the CRL will result in timely approval of intranasal naloxone or approval at all. Intranasal Epinephrine Intranasal epinephrine, a prescription epinephrine nasal spray product candidate, is intended to be used for emergency treatment of allergic reactions, including anaphylaxis to stinging insects, allergen immunotherapy, foods, drugs and other allergens. Other Proprietary Product Candidates In addition to intranasal naloxone and intranasal epinephrine, the company has two other proprietary product candidates in development. These product candidates incorporate multiple indications utilizing a wide variety of the company’s technical capabilities. APIs The company began to manufacture and sell two API products, Recombinant Human Insulin, or RHI API, and porcine insulin API, as a result of the company’s acquisition of Merck Sharpe & Dohme’s, or Merck’s, API manufacturing business in Eragny-sur-Epte, France, or the Merck API Transaction, in April 2014. The purpose of the acquisition was to enhance the company’s vertical integration strategy as the company targets certain finished products for the injectable insulin market. However, the company continues to sell RHI API and porcine insulin API to third parties, which helps fund the company’s vertical integration strategy. Supply Agreement with MannKind Corporation On July 31, 2014, the company entered into a supply agreement with MannKind Corporation, or MannKind, or the Supply Agreement, pursuant to which the company agreed to manufacture for and supply to MannKind certain quantities of RHI API for use in MannKind’s product Afrezza. Sales and Marketing The company’s products are primarily marketed and sold to institutions, such as hospitals, long-term care facilities, alternate care sites, clinics, and doctors’ offices. Additionally, the company sells to retail pharmacies. Most institutional customers are members of one or more group purchasing organizations, which negotiate collective purchasing agreements on behalf of their members. These facilities purchase products through specialty distributors and wholesalers. The company has relationships with the major group purchasing organizations in the United States. The company also has relationships with major specialty distributors, wholesalers and retailers who distribute pharmaceutical products nationwide. The company’s major customers and partners are AmerisourceBergen Corporation, McKesson Corporation, and Cardinal Health, Inc. The company’s marketing department is responsible for establishing and maintaining contracts and relationships with the group purchasing organizations, distributors, retailers, wholesalers and, occasionally, directly with hospitals or long-term care facilities. One or more of the company’s proprietary product candidates may require deployment of a sales force either directly or through a strategic partner. Competition The company face significant competition for its products and product candidates from pharmaceutical companies that focus on the generic injectable and inhalation markets, such as Pfizer, Inc., Eli Lilly and Co., Sagent Pharmaceuticals, Inc., Akorn, Inc., Sandoz Inc., Viatris Inc., Fresenius Kabi USA, Nexus Pharmaceuticals, Apotex Corp, Amneal Biosciences, American Regent Inc., Hikma Pharmaceuticals USA, Inc., Par Pharmaceuticals, Cipla USA Inc., Meitheal Pharmaceuticals, Dr. Reddy’s Laboratories, Inc., Sun Pharmaceuticals, Inc., Accord Healthcare Ltd., Amring Pharmaceuticals, Bausch Health, Zydus Pharmaceuticals USA Inc., AuroMedics Pharma LLC, and Teva Pharmaceutical Industries Ltd. Government Regulation In the United States, the federal agencies that regulate the company’s facilities, operations, employees, products (including their manufacture, sale, import and export) and services include: the U.S. Food and Drug Administration, the Drug Enforcement Agency, the Environmental Protection Agency, the Occupational Health & Safety Administration, the Department of Agriculture, the Department of Labor, the Department of Defense, Customs and Border Protection, the Department of Commerce, the Department of Treasury and others. Many of the company’s activities are subject to the jurisdiction of other federal regulatory and enforcement departments and agencies, such as the Department of Health and Human Services, or HHS, Office of the Inspector General, or OIG, the Federal Trade Commission (which also has the authority to regulate the advertising of consumer healthcare products, including over-the-counter drugs), the Department of Justice, the Drug Enforcement Administration, or DEA, the Veterans Administration, the Centers for Medicare and Medicaid Services and the Securities and Exchange Commission, or SEC. The company and its suppliers are required to comply with applicable FDA manufacturing requirements contained in the FDA’s cGMP regulations. The company and its suppliers are subject to periodic inspections of facilities by the FDA and other authorities to assess the company’s compliance with applicable regulations. The company is subject to the Open Payment Act. As a life sciences company, the company is subject to the federal anti-kickback statute, or AKS. The company is subject to federal, state and local environmental laws and regulations, both the U.S. and foreign, including those promulgated by the Occupational Safety and Health Administration, the Environmental Protection Agency, the Department of Health and Human Services and the Air Quality Management District, which govern activities and operations that may have adverse environmental effects, such as discharges to air, soil and water, as well as handling and disposal practices for solid and hazardous wastes. The company also must comply with data protection and data privacy requirements, such as HIPAA, GDPR, CCPA, and the upcoming CPRA. Each of Amphastar and the company’s U.S.-based subsidiaries subject to or covered by DSCSA comply with the new requirements. Intellectual Property The company owns several U.S. and foreign patents covering processes and equipment used in the manufacture of a few of the company’s products. The expiration dates of these patents range from 2024 to 2039. The company also owns several trademarks registered with the USPTO. The company owns a U.S. patent covering the HFA version of Primatene MIST: U.S. Patent Number 8,367,734, which was issued on February 5, 2013, and expires in January 2026. The company has several patent applications that are pending. Research and Development The company’s research and development expense was $74.8 million for the year ended December 31, 2022. History Amphastar Pharmaceuticals, Inc., a California corporation, was founded in 1996. The company was incorporated in 2004.